IL-36γ signalling promotes a proinflammatory macrophage state that is associated with reduced lipid uptake
Bibliographic record
Abstract
Macrophages exhibit remarkable functional plasticity, adopting immune activating or immune suppressive states in response to environmental cues. While these phenotypic shifts are essential to immune homeostasis, the mechanisms whereby they are regulated in humans are poorly understood. Here, we investigated the role of interleukin (IL)-36γ, a barrier cytokine that is strongly induced in response to infection. We show that IL-36γ signalling modifies the anti-inflammatory phenotype of human alternatively activated (M2a) macrophages, by decreasing the expression the CD163 M2 marker. This change was accompanied by the upregulation of M1 surface markers (CD40, CD80) and M1 cytokines (e.g. TNFα, CXCL8). IL-36γ treatment of M2a macrophages also reduced the expression of TREM2 and CD36, two lipid-binding receptors that sustain the energy requirements of the M2 state. Accordingly, we also observed a decrease in the uptake of CD36 and TREM2 ligands (oxidized low-density lipoproteins). These findings indicate that IL-36γ shifts the immune and metabolic profile of M2a macrophages towards an M1-like state.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".